Antidepressants Flashcards
What are the main types of antidepressants?
- Selective serotonin reuptake inhibitors (SSRIs)
- Serotonin and noradrenaline reuptake inhibitors (SNRIs)
- Tricyclic antidepressants (TCAs)
- Others (mirtazapine and vortioxetine)
How do SSRIs work?
Block the reuptake of serotonin by the Presynpatic membrane on the axon terminal
Causes more serotonin in the synapses in the CNS, boosting communication between neurones
Can lead to down-regulation of post-synaptic serotonin receptors
How do SNRIs work?
Blocking the reuptake of serotonin and NorAd by the presynaptic membrane
More serotonin and NorAd in synapses in the CNS
How do Tricyclic antidepressants work?
Block reuptake of serotonin and NorAd by presynaptic membrane
Block ACh and histamine receptors giving them anticholinergic and sedative side effects
What are the common ACh (muscarinic) effects?
- Dry mouth
- Thirst
- Difficulty urinating
- Urinary retention
- Dry skin
- Hot and flushed skin
What are the common Histamine effects?
- Dry mouth
- Drowsiness
- Dizziness
- Nausea and vomiting
What are the common Adrenaline/NorAd effects?
- Sweating
- Tremor
- Headaches
- Nausea
- Dizziness
What are some examples of SSRIs?
Sertraline
Citalopram
Escitalopram
Fluoxetine
Paroxetine
Outline sertraline
Anti-anxiety effects
Considered one of the safest in patients with heart disease
Higher rate of diarrhoea
Outline citalopram
Can prolong QT interval (dose dependent)
QT prolongation can cause torsades de pointes
Along with escitalopram, least safe SSRI in patients with heart disease (still safer than TCAs)
Why is fluoxetine the first-line choice in children and adolescents?
Long half-life of 4-7 days
Remains active in the body long after stopping
What can paroxetine cause?
Weight gain
Discontinuation symptoms
What are the key side effects of SSRIs?
GI symptoms
Headaches
Sexual dysfunction
Hyponatraemia
Anxiety or agitation
Increased suicidal thoughts, suicide risk, self-harm
Increased bleeding risk (especially with anticoags or NSAIDs)
What are some examples of SNRIs?
Duloxetine
Venlafaxine
What are some side effects of SNRIs?
Similar to SSRIs
Increased blood pressure
Contraindicated in uncontrolled hypertension
When is venlafaxine used?
Inadequate response to other antidepressants
- More likely to cause discontinuation symptoms when stopped
- Increased risk of death from O.D
- Must measure blood pressure
What are some examples of TCAs?
Amitriptyline
Nortriptyline
Used at low dose for neuropathic pain (this dose is too low to treat depression)
What are TCAs known to cause?
Arrhythmias e.g.
- Tachycardia
- Prolonged QT interval
- Bundle branch block
- Dry mouth
- Urinary retention
What should patients be warned about when taking TCAs?
Blurred vision espeically if they drive or operate heavy machinery
Due to antimuscarinic properties of TCAs
Why are TCAs taken at night?
Due to its anticholinergic effects it also causes sedation
What are the side effects of Mirtazapine?
Sedation
Increased appetite
Weight gain
Taken at night due to sedative effect
(Greatest effect at low doses e.g. 15mg, less present at high doses e.g. 45mg)
Less likely to cause sexual dysfunction
How does mirtazapine work?
5HT-2 and 5HT-3 antagonist
Strong H1 activity- causes the sedation
How can side effects be beneficial to different patients? e.g. Mirtazapine
If a patient is struggling to sleep, with weight loss then the side effects causing sedation and increased appetite can be helpful for the patient
This is why mirtazapine is more useful in older patients, however, in overweight oversleeping patients it is not useful
When is vortioxetine used?
Third-line treatment after inadequate response to two other antidepressants
Acts as SSRI and also stimulates and blocks various types of serotonin receptors
Considered safe with heart disease, commonly causes nausea for first few weeks
What are monoamine oxidase inhibitors?
MAOI-A, works on serotonin break down enzymes, so there is an increase in serotonin in the terminal
MAOI-B, works on dopamine break down enzymes, increase in dopamine in the terminal
Both can cause an increase in adrenaline
When are MAOIs favoured?
Atypical depression
What are some examples of irreversible MAOIs?
Phenelzine
Isocarboxazid
More dangerous
What are some examples of reversible MAOIs?
Moclobamide
Tranylcypromine
Less dangerous
What must be considered when giving MAOIs?
- Potential for significant and dangerous interactions with other drugs
- Tyramine reaction leading to hypertensive crisis
What must be avoided to prevent a tyramine reaction?
Cheese
Pickled meats
Wine
How can you change MAOIs to another antidepressant?
6 week washout period
What is the most common side effect of vortioxetine?
Nausea
When is vortioxetine used?
Difficult to treat cognitive symptoms
What can occur in the period of starting an antidepressant?
Increased :
- Agitation
- Anxiety
- Suicidal thoughts
- Acts of suicide
Particular problem in younger patients
When should patients be reviewed after starting antidepressants?
18-25
Within one week (due to increased risk of suicide)
Over 25
Within two weeks
Normally a noticeable response within 2-4 weeks of treatment, with inadequate response the next step is to consider increasing dose or changing treatment
When starting treatment for depression for the first time, when should an SNRI be considered?
Comorbid neuropathic pain
In depression when do you increase or switch antidepressants?
No benefit- switch
Partial benefit - increase dose
In anxiety when do you increase or switch antidepressants?
Increase dose if no initial benefit
What antidepressants can be directly switched?
SSRIs and SNRIs (except fluoxetine due to long half-life)
How do you switch between an SSRI and other antidepressants e.g. mirtazapine?
Cross-tapered over several weeks
Gradually reducing dose of existing drug while increasing dose of new one
What can happen if antidepressants are stopped too suddenly?
Once started they should be continued for at least 6 months before stopping (2 years in recurrent depressing)
Stopping too early can cause depression to return
How should antidepressants be stopped?
Dose should be slowly reduced over at least 4 weeks to minimise discontinuation symptoms
What are discontinuation symptoms?
2-3 days after stopping treatment
Resolves within 1-2 weeks
Flu-like symptoms
Electric shock-like sensations
Irritability
Insomnia
Vivid dreams
What influences discontinuation syndrome?
Half-life
Shorter half-life, bigger the problem
What medications are the most responsible for discontinuation syndrome?
Paroxetine
Venlafaxine
How can you deal with discontinuation syndrome?
Alternate days or taking
Snap tablets in half
If very difficult, switch to fluoxetine, then reduce and stop that
What is serotonin syndrome?
Mild to severe and potentially life-threatening symptoms
Caused by excessive serotonin activity
Usually occurs with higher doses of antidepressants and when multiple are used together
What are the symptoms of serotonin syndrome?
Altered mental state
- Anxiety
- Agitation
Autonomic nervous system hyperacitivty
- Tachycardia
- Hypertension
- Hyperthermia
Neuromuscular hyperactivity
- Hyperreflexia
- Tremor
- Rigidity
Why is severe serotonin syndrome a medical emergency?
- Confusion
- Seizures
- Severe hyperthermia
- Respiratory failure
How is severe serotonin syndrome treated?
- Supportive care e.g. benzodiazepines for sedation
- Withdrawal of causative medications
- Aggressive fluid treatment
- Cryptoheptadine
In alcoholic dependents with serotonin syndrome why do you give pabrinex first before glucose?
Thiamine is a cofactor for glucose metabolism
So when glucose is broken down this increases thiamine deficit, worsening thiamine deficiency
